Evaluation of β-cell function is of interest in many different situations: in monitoring diabetic subjects under treatment, in family studies estimating the risk of developing diabetes, and after pancreas or islet transplantation. The exact β-cell mass cannot be measured directly. As a surrogate, the glucagon test has gained wide acceptance as a measure of β-cell function during daily life since the plasma C-peptide concentration 6 minutes after 1 mg of glucagon (I.V.) has been shown, in most cases, to correspond to the maximal C-peptide concentration after a standard meal (Faber O K, Binder C (1977) C-peptide response to glucagon. A test for the residual beta-cell function in diabetes mellitus. Diabetes 26:605-610; Madsbad S, Krarup T, McNair P et al (1981) Practical clinical value of the C-peptide response to glucagon stimulation in the choice of treatment in diabetes mellitus. Acta Med. Scand. 210:153-156). Estimation of maximal secretory capacity has been made using the technically demanding and long-lasting hyperglycemic clamp with infusion of 5 g L-arginine (Ward W K, Bolgiano D C, McKnight B, Halter J B, Porte D (1984) Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J.Clin.Invest. 74:1318-1328). However, this test is time consuming and known to cause considerable patient discomfort and pain.
Impaired glucose tolerance (IGT) is common in the U.S. population. The prevalence of impaired glucose tolerance increases from 11% in the general population aged 20-74 years to 24% in those 40-75 years of age with a family history of diabetes and a body weight greater than 120% of normal. Subjects with impaired glucose tolerance are at high risk for the development of cardiovascular disease as well as non-insulin dependent diabetes mellitus (NIDDM), also known as Type 2 diabetes.
Impaired glucose tolerance is characterized by early subtle defects in pancreatic β-cell function, accompanied by insulin resistance. These early defects include an impaired ability of the β-cell to sense and respond to small changes in plasma glucose concentrations with appropriate levels of insulin secretion, and a mild shift to the right of the glucose insulin secretion dose-response curve. The glucose sensing and fast insulin secretion response abilities of the β-cell are lost very early in the course of IGT when 2-hour glucose levels are minimally elevated. The deterioration of glucose control in IGT with time is predominantly due to progressive impairment of β-cell function, and in many cases results in the definitive loss of glucose control and the deleterious onset of NIDDM.
From the above background it can be seen that there is a real and continuing need for a quick and easy test to measure β-cell function as a marker impaired glucose tolerance test that is reliable and without significant adverse side effects and/or patient pain and discomfort. This invention has as its primary objective the fulfillment of this continuing need.